Fungal biotransformation of tanshinone results in [4+2] cycloaddition with sorbicillinol: evidence for enzyme catalysis and increased antibacterial activity

The biotransformation of tanshinone IIA to a new antibacterial agent tanshisorbicin (1) by the fungus Hypocrea sp. (AS 3.17108) is described. The structure of tanshisorbicin is a hybrid of tanshinone IIA (2) and sorbicillinol (3). The latter is a metabolite produced by Hypocrea sp. The structure of tanshisorbicin was determined using mass spectrometry, NMR spectroscopy, and ECD calculations. The anti-MRSA activity of 1 was found to be significantly higher than that of the parent substrate Tan IIA. Preliminary experiments indicate that tanshisorbicin is formed via a [4+2] cycloaddition reaction that is likely catalyzed by microbial enzyme.